Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Optimizing cardiovascular disease mortality prediction: a super learner approach in the tehran lipid and glucose study.

BACKGROUND & AIM: Cardiovascular disease (CVD) is the most important cause of death in the world and has a potential impact on health care costs, this study aimed to evaluate the performance of machine learning survival models and determine the optimum model for predicting CVD-related mortality. METHOD: In this study, the research population was all participants in Tehran Lipid and Glucose Study (TLGS) aged over 30 years. We used the Gradient Boosting model (GBM), Support Vector Machine (SVM), Super Learner (SL), and Cox proportional hazard (Cox-PH) models to predict the CVD-related mortality using 26 features. The dataset was randomly divided into training (80%) and testing (20%). To evaluate the performance of the methods, we used the Brier Score (BS), Prediction Error (PE), Concordance Index (C-index), and time-dependent Area Under the Curve (TD-AUC) criteria. Four different clinical models were also performed to improve the performance of the methods. RESULTS: Out of 9258 participants with a mean age of (SD; range) 43.74 (15.51; 20-91), 56.60% were female. The CVD death proportion was 2.5% (228 participants). The death proportion was significantly higher in men (67.98% M, 32.02% F). Based on predefined selection criteria, the SL method has the best performance in predicting CVD-related mortality (TD-AUC > 93.50%). Among the machine learning (ML) methods, The SVM has the worst performance (TD-AUC = 90.13%). According to the relative effect, age, fasting blood sugar, systolic blood pressure, smoking, taking aspirin, diastolic blood pressure, Type 2 diabetes mellitus, hip circumference, body mss index (BMI), and triglyceride were identified as the most influential variables in predicting CVD-related mortality. CONCLUSION: According to the results of our study, compared to the Cox-PH model, Machine Learning models showed promising and sometimes better performance in predicting CVD-related mortality. This finding is based on the analysis of a large and diverse urban population from Tehran, Iran.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study.

BACKGROUND: Elevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels. METHODS: This prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value. RESULTS: During a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01-1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04-1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95-1.46) in normoglycemic and 1.32 (95% CI: 0.98-1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12-1.64) and 1.57 (95% CI: 1.22-2.03), respectively. CONCLUSIONS: The difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Gender differences in midlife to later-life cumulative burden and variability of obesity measures and risk of all-cause and cause-specific mortality.

BACKGROUND/OBJECTIVES: Previous studies have reported the gender-specific association between general and central obesity measures, using snapshot assessments, and mortality events. This study seeks to further explore this link by examining how the longitudinal cumulative burden and variability of obesity measures from midlife to later-life impact mortality events in the Atherosclerosis Risk in Communities (ARIC) study population, specifically in relation to gender differences. SUBJECTS/METHODS: Using data from the ARIC study, a total of 7615 (4360 women) participants free of cardiovascular disease, cancer, and early mortality events were included in the data analysis. Longitudinal cumulative burden (estimated by the area under the curve (AUC) using a quadratic mixed-effects method) and variability (calculated according to average successive variability (ASV)) were considered as exposures, separately and all together. Cox proportional hazard regression models were used to estimate multivariable-adjusted standardized hazard ratios. RESULTS: The mean age was 62.4 and the median follow-up was 16.9 years. In men, AUCs of waist-related obesity measures, and also ASVs of all obesity measures were associated with increased all-cause mortality risk. In women, waist circumference and waist-to-height ratio AUCs were associated with increased all-cause mortality risk. Regarding cardiovascular mortality, all adiposity measures ASVs in both genders and waist-related obesity measures AUCs in men were associated with increased risk. Significant gender differences were found for the associations between cumulative and variability of waist-to-hip ratio for all-cause mortality and all adiposity measures ASVs for cardiovascular mortality risk with higher impact among men. CONCLUSIONS: Cumulative burden and variability in general and central obesity measures were associated with higher all-cause and cardiovascular mortalities among men. In women, general obesity measures variability, as well as cumulative and variability of central adiposity measure, increased all-cause mortality risk.

Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis.

BACKGROUND: To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions. METHODS AND RESULTS: In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long-term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both P<0.001) but not coronary artery calcium in the multivariable-adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1-SD increase in systolic BP (OR, 1.50 [95% CI, 1.19-1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19-1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood. CONCLUSIONS: Long-term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.

Factors associated with smoking intensity among adult smokers: findings from the longitudinal cohort of the Tehran lipid and glucose study.

BACKGROUND: Smoking is a significant public health problem, and there is a scarcity of documents regarding its severity, particularly in developing countries. This study aimed to determine factors related to the number of cigarettes consumed daily by adult smokers in Tehran. METHODS: This study was conducted within the framework of the longitudinal study of Tehran Lipid and Glucose Study (TLGS). The study included 786 adult smokers living during four consecutive follow-ups from 2005 to 2016. The intensity of smoking was measured by the number of cigarettes consumed daily by adult smokers. Data analysis was done longitudinally and based on the mixed effects zero-inflated discrete Weibull (ZIDW) regression model. RESULTS: The mean age of the individuals was 40.35 ± 12.68 years, and 643 (81.8%) of them were men. Also, 52.7% of individuals were daily smokers, 15.6% were occasional smokers, and 31.7% were non-smokers who became smokers during the study. Variables of age 1.005 (95%CI: 1.001-1.008), gender of male 1.196 (95%CI: 1.051-1.39), and marital status (divorced/widowed vs. single) 1.168 (95%CI: 1.015-1.39) were positively associated with smoking intensity. Education level (master and higher vs. illiterate) 0.675 (95%CI: 0.492-0.926)), employment status (student vs. unemployed) 0.683 (95%CI: 0.522-0.917), (housewife vs. unemployed) 0.742 (95%CI: 0.606-0.895), (Unemployed with income vs. unemployed) 0.804 (95%CI: 0.697, 0.923), implementation of smoking prohibition regulations (yes vs. no) 0.88 (95%CI: 0.843-0.932), and history of cardiovascular disease in male relatives (yes vs. no) 0.85 (95%CI: 0.771-0.951) were associated with lower smoking intensity. CONCLUSION: We showed that demographic factors are associated with the intensity of smoking among adults and should be considered in policymakers' intervention programs to reduce smoking and quit smoking.

The effect of smoking on latent hazard classes of metabolic syndrome using latent class causal analysis method in the Iranian population.

BACKGROUND: The prevalence of metabolic syndrome is increasing worldwide. Clinical guidelines consider metabolic syndrome as an all or none medical condition. One proposed method for classifying metabolic syndrome is latent class analysis (LCA). One approach to causal inference in LCA is using propensity score (PS) methods. The aim of this study was to investigate the causal effect of smoking on latent hazard classes of metabolic syndrome using the method of latent class causal analysis. METHODS: In this study, we used data from the Tehran Lipid and Glucose Cohort Study (TLGS). 4857 participants aged over 20 years with complete information on exposure (smoking) and confounders in the third phase (2005-2008) were included. Metabolic syndrome was evaluated as outcome and latent variable in LCA in the data of the fifth phase (2014-2015). The step-by-step procedure for conducting causal inference in LCA included: (1) PS estimation and evaluation of overlap, (2) calculation of inverse probability-of-treatment weighting (IPTW), (3) PS matching, (4) evaluating balance of confounding variables between exposure groups, and (5) conducting LCA using the weighted or matched data set. RESULTS: Based on the results of IPTW which compared the low, medium and high risk classes of metabolic syndrome (compared to a class without metabolic syndrome), no association was found between smoking and the metabolic syndrome latent classes. PS matching which compared low and moderate risk classes compared to class without metabolic syndrome, showed that smoking increases the probability of being in the low-risk class of metabolic syndrome (OR: 2.19; 95% CI: 1.32, 3.63). In the unadjusted analysis, smoking increased the chances of being in the low-risk (OR: 1.45; 95% CI: 1.01, 2.08) and moderate-risk (OR: 1.68; 95% CI: 1.18, 2.40) classes of metabolic syndrome compared to the class without metabolic syndrome. CONCLUSIONS: Based on the results, the causal effect of smoking on latent hazard classes of metabolic syndrome can be different based on the type of PS method. In adjusted analysis, no relationship was observed between smoking and moderate-risk and high-risk classes of metabolic syndrome.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Association of physical activity with increased PI3K and Akt mRNA levels in adipose tissues of obese and non-obese adults.

Phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway regulates glucose and lipid metabolism. We examined the association of PI3K and Akt expression in visceral (VAT) and subcutaneous adipose tissue (SAT) with daily physical activity (PA) in non-diabetic obese and non-obese adults. In this cross-sectional study, we included 105 obese (BMI ≥ 30 kg/m2) and 71 non-obese (BMI < 30 kg/m2) subjects (aged/ ≥ 18 years). PA was measured using a valid and reliable International Physical Activity Questionnaire(IPAQ)-long-form, and the metabolic equivalent of task(MET) was calculated. Real-time PCR was performed to analyze the mRNA relative expression. VAT PI3K expression had a lower level in obese compared to non-obese (P = 0.015), while its expression was higher in active individuals than inactive ones (P = 0.029). SAT PI3K expression was increased in active individuals compared to inactive ones (P = 0.031). There was a rise in VAT Akt expression in the actives compared to the inactive participants (P = 0.037) and in non-obese/active compared to non-obese/inactive individuals (P = 0.026). Obese individuals had a decreased expression level of SAT Akt compared to non-obsesses (P = 0.005). VAT PI3K was directly and significantly associated with PA in obsesses (ß = 1.457, P = 0.015). Positive association between PI3K and PA suggests beneficial effects of PA for obese individuals that can be partly described by PI3K/Akt pathway acceleration in adipose tissue.

Data-driven phenomapping for novel classification for cardiovascular outcomes compared with traditional obesity index: Tehran Lipid and Glucose Study.

OBJECTIVE: This study aimed to propose a data-driven framework for classification of at-risk people for cardiovascular outcomes regarding obesity and metabolic syndrome. DESIGN: A population-based prospective cohort study with a long-term follow-up. SETTING: Data from the Tehran Lipid and Glucose Study (TLGS) were interrogated. PARTICIPANTS: 12 808 participants of the TLGS cohort, aged ≥20 years who have followed for over 15 years were assessed. MAIN OUTCOME MEASURES: Data for 12 808 participants, aged ≥20 years who have followed for over 15 years, collected through TLGS as a prospective, population-based cohort study, were analysed. Feature engineering followed by hierarchical clustering was used to determine meaningful clusters and novel endophenotypes. Cox regression was used to demonstrate the clinical validity of phenomapping. The performance of endophenotype compared with traditional classifications was evaluated by the value of Akaike information criterion/Bayesian information criterion. R software V.4.2 was employed. RESULTS: The mean age was 42.1±14.9 years, 56.2% were female, 13.1%, 2.8% and 6.2% had experienced cardiovascular disease (CVD), CVD mortality and hard CVD, respectively. Low-risk cluster compared with the high risk had significant difference in age, body mass index, waist-to-hip ratio, 2 hours post load plasma glucose, triglyceride, triglycerides to high density lipoprotein ratio, education, marital status, smoking and the presence of metabolic syndrome. Eight distinct endophenotypes were detected with significantly different clinical characteristics and outcomes. CONCLUSION: Phenomapping resulted in a novel classification of population with cardiovascular outcomes, which can, better, stratify individuals into homogeneous subclasses for prevention and intervention as an alternative of traditional methods solely based on either obesity or metabolic status. These findings have important clinical implications for a particular part of the Middle Eastern population for which it is a common practice to use tools/evidence derived from western populations with substantially different backgrounds and risk profiles.

Identifying Factors Related to Serum Lipids Using Multilevel Quantile Model: Analysis of Nationwide STEPs Survey 2016.

Background: Lipid disorder is a modifiable risk factor for diseases related to plaque formation in arteries such as heart attack, stroke, and peripheral vascular diseases. Identifying related factors and diagnosis and treatment in time reduces the incidence of non-communicable diseases (NCDs). The aim of this study was to determine factors associated with lipids based on a national survey data. Methods: Data of 16757 individuals aged 25-64 years obtained from the Iranian STEPwise approach to NCD risk factor surveillance (STEPs) performed in 2016, through multistage random sampling, were analyzed. Because of clustered, hierarchical, and skewed form of the data, factors related to total holesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol) (LDL-C), high-density lipoprotein-cholesterol) (HDL-C), TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C were determined applying multilevel quantile mixed model. Parameters of the model were estimated on the basis of random effect of the province as well as urban or rural area for 10th, 25th, 50th, 75th, and 90th quantiles. Statistical analyses were performed by R software version 4.0.2. Results: Significant relationship was found between age, body mass index (BMI), waist circumference (WC), diabetes, hypertension, smoking, physical activity, education level, and marital status with TC, LDL-C, HDL-C, LDL-C, and LDL-C/HDL-C. With increasing BMI and WC, subjects had higher levels of serum lipids, especially in higher quantiles of lipid levels. Lipid levels were significantly increased among smokers and those with diabetes or hypertension. The random effects were also significant showing that there is a correlation between the level of lipids in provincial habitants as well as urban and rural areas. Conclusions: This study showed that the effect of each factor varies depending on the centiles of the lipids. Significant relationship was found between sociodemographic, behaviors, and anthropometric indices with lipid parameters.

Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Longitudinal Associations Between TPO Gene Variants and Thyroid Peroxidase Antibody Seroconversion in a Population-Based Study: Tehran Thyroid Study.

Introduction: Autoimmune thyroid diseases (AITD) are usually accompanied by anti-thyroid antibodies which can serve as early predictive markers. This study was designed to investigate the relationship between thyroid peroxidase (TPO) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. Methods: Participants from phases 1 and 2 of the Tehran Thyroid Study in (n = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the TPO gene (cross-sectional approach). TPOAb-negative participants (n = 4815) were followed up for seroconversion for 5.5 years. The relationship between the TPO gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). Results: There were 521 TPOAb-positive participants in the cross-sectional phase and 266 new TPOAb-positive cases observed during the follow-up period. After quality control (Hardy-Weinberg equilibrium (p < 1 × 10-5) and minor allele frequency < 0.05), 49 SNPs were qualified for association analyses. From this set fourteen SNPs were identified that were associated with TPOAb positivity. rs6605278, located in the 3'UTR TPO gene, was the most highly significantly associated of the variant and remained associated after adjustment for age, gender, body mass index (BMI), smoking, number of parity, and oral contraceptive consumption in both cross-sectional and longitudinal analyses (p < 0.05). Conclusions: TPOAb-positivity can be partially explained by variants in the TPO gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.

A 10-Year Cardiovascular Risk in Adults with Different Levels of Spiritual Health: Tehran Lipid and Glucose Study.

Background: Previous studies have shown that spiritual experience may reduce cardiovascular disease (CVDs). However, little is known about the relationship between spiritual health and the gender-specific risk of CVDs in communities with different cultures. Methods: A total of 3249 individuals (53.7% female, 75.0% middle-aged) participated in the Tehran Lipid and Glucose Study (TLGS) from 2015 to 2017 were included. Based on the ACC/AHA pooled cohort equation, CVD risk over ten years was examined. Spiritual health was measured using a developed tool for measuring spiritual health in Muslim populations (SHIMA-48). Linear regression models were used to assess the association between spiritual health and ACC/AHA risk scores. The natural logarithm scale was calculated to consider the normal distribution hypothesis of the regression model. Results: The current results suggest a slight but significant increase in the mean of spiritual health in women compared to men in both cognitive/emotional and behavioral dimensions (P < 0.001). In both sexes, a higher prevalence of smoking was observed in participants with lower levels of spiritual health (P < 0.004). In men, compared to those with a low level of spiritual health (the first tertile), the logarithm of the ACC-AHA risk score was reduced by 0.11 (P = 0.004) and 0.18 (P < 0.001) for those in the second and third tertiles of spiritual health, respectively. This result may be attributed to higher cigarette smoking among the latter group. Similar results were not observed in women. Conclusions: Current results indicate a gender-specific association between spiritual health and cardiovascular disease risk. Our findings imply that promoting spiritual health can be considered an effective strategy in future preventive interventions, primarily by controlling the desire to smoke in men.

Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis.

BACKGROUND: We aimed to assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes (T2DM) during an 18-year follow-up. METHODS: The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: (1) normal FPG (NFG) to NFG (reference category); (2) NFG to impaired fasting glucose (IFG) (i.e., 126 > FPG ≥ 100 mg/dl); (3) NFG to T2DM; (4) IFG to NFG; (5) IFG to IFG; (6) IFG to T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia was used to estimate hazard ratios (HRs (95% CI)) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated. RESULTS: During follow-up, 2,362 all-cause mortality events were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95%CI 1.24 (0.98-1.57), p = 0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM group were at increased risk for CV mortality (2.21 (1.42-3.44)). We also found that women in NFG-IFG (1.52 (1.20-1.91)), NFG-T2DM (2.90 (1.52-5.51)), and IFG-IFG (1.30 (1.02-1.66)) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 (1.15-2.74)) and IFG-T2DM (1.34 (1.04-1.72)). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts (RHR; 1.24 (1.01-1.54)). After further adjustment for physical activity, results were in line with the main findings, excluding T2DM up to six years after the measurement period and early mortality events. CONCLUSION: In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality.

Determinants of the progression to type 2 diabetes and regression to normoglycemia in people with pre-diabetes: A population-based cohort study over ten years.

AIMS: To determine the rates and predictors of the regression to normoglycemia and progression to diabetes among subjects with pre-diabetes. METHODS: A 10-year longitudinal population-based study was conducted among 1329 participants with pre-diabetes in the Tehran Lipid and Glucose Study. Pre-diabetes was divided into isolated IFG (iIFG), isolated IGT (iIGT), and combined IFG/IGT. Univariate and stepwise multivariable Cox regression was used to evaluate predictors of glycemic conversions. RESULTS: The cumulative incidences of normoglycemia and diabetes were 43.7% (95%CI 40.9-46.4) and 40.1% (37.3-42.7), respectively. Isolated IGT returned to normoglycemia more than iIFG (HR:1.26, 1.05-1.51), but there was no difference in how quickly they progressed to diabetes. Regression to normoglycemia was associated with younger age, female sex, lower BMI, no familial history of diabetes, higher HDL-C, and ex-smoking. Older age, higher BMI, diastolic blood pressure, total cholesterol, lower HDL-C, and familial history for diabetes were associated with progression to diabetes. The influence of BMI on glycemic status conversions diminished with age. At approximately above 60 years old, the hazards of BMI for any conversions faded out. CONCLUSIONS: The modifiable predictors of regression to normoglycemia and progression to diabetes are roughly the same. The importance of BMI attenuates in elderly subjects.

Type 2 diabetes remission after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and one anastomosis gastric bypass (OAGB): results of the longitudinal assessment of bariatric surgery study.

BACKGROUND: Several studies on various bariatric surgeries involving patients with type 2 diabetes mellitus (T2DM) showed an overall rate of remission of hyperglycemia. However, there is little known about predictive factors on remission after different types of surgeries. The aim of this study was to identify the T2DM remission rate and to determine the effects of preoperative factors characteristics of remission of type 2 diabetes in Iran. METHODS: We conducted a retrospective analysis of 1351 patients with T2DM operated by three different types of surgeries (Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and One Anastomosis Gastric Bypass (OAGB)). Diabetes remission was defined according to the American Diabetes Association (ADA) criteria. Binary logistic regression analyses were employed. RESULTS: A total of 1351 patients, 675 patients (50.0%) undergoing OAGB, 475 (35.2%) RYGB, and 201 (14.9%) SG. 80.6%, 84.2% of OAGB, 81.7%, 82.6% of RYGB, and 77.1%, 81.5% of SG participants were in T2DM remission after 1 and 3 years, respectively. 1- and 3-year remission were associated with preoperative age, duration of T2DM, FBS and HbA1c, BMI, insulin therapy, and a family history of obesity (p < 0.05). CONCLUSION: The remission of T2DM after RYGB, SG, and OAGB surgery is dependent on various preoperative factors. Patients with younger age, shorter duration of T2DM, lower preoperative HbA1c and FBS, higher BMI, who were not on insulin therapy, and not having a family history of obesity were the best candidates to achieve a prolonged diabetes remission.

Incidence and risk factors of severe non-proliferative/proliferative diabetic retinopathy: More than a decade follow up in the Tehran Lipids and Glucose Study.

AIMS/INTRODUCTION: To examine the incidence rate of severe non-proliferative and proliferative diabetic retinopathy (severe-NPDR/PDR) and determine its potential risk factors. MATERIALS AND METHODS: The study consisted of 1,169 participants (675 women) with type 2 diabetes mellitus, aged ≥20 years. A trained interviewer collected information about the history of pan-retinal photocoagulation as a result of diabetic retinopathy. Multivariable Cox proportional hazards regression models were applied. RESULTS: We found 187 cases (126 women) of severe-NPDR/PDR during a median follow-up period of 12.7 years; the corresponding incidence rate was 13.6 per 1,000 person-years. Being overweight (hazard ratio [HR], 95% confidence interval [CI] 0.60, 0.39-0.92) and obese (HR 0.48, 95% CI 0.27-0.83) were associated with lower risk, whereas being smoker (HR 1.75, 95% CI 1.12-2.74), having fasting plasma glucose levels 7.22-10.0 mmol/L (HR 2.81, 95% CI 1.70-4.62), fasting plasma glucose ≥10 mmol/L (HR 5.87, 95% CI 3.67-9.41), taking glucose-lowering medications (HR 2.58, 95% CI 1.87-3.56), prehypertension status (HR 1.65, 95% CI 1.05-2.58) and newly diagnosed hypertension (HR 1.96, 95% CI 1.06-3.65) increased the risk of severe-NPDR/PDR. Among newly diagnosed diabetes patients, being male was associated with a 59% lower risk of severe-NPDR/PDR (HR 0.41, 95% CI 0.21-0.79). Furthermore, patients who had an intermediate level of education (6-12 years) had a higher risk of developing PDR (HR 1.86, 95% CI 1.05-3.30) compared with those who had <6 years of education. CONCLUSIONS: Among Iranians with type 2 diabetes mellitus, 1.36% developed severe-NPDR/PDR annually. Normal bodyweight, being a smoker, out of target fasting plasma glucose level, prehypertension and newly diagnosed hypertension status were independent risk factors of severe-NPDR/PDR. Regarding the sight-threatening entity of advanced diabetic retinopathy, the multicomponent strategy to control diabetes, abstinence of smoking and tight control of blood pressure should be considered.

The Effects of Smoking on Metabolic Syndrome and Its Components Using Causal Methods in the Iranian Population.

BACKGROUND: The aim of this study was to estimate the effect of smoking on metabolic syndrome (MS) and its components applying inverse probability-of-treatment weighting (IPTW) and propensity score (PS) matching. METHODS: Using data from Tehran Lipid and Glucose Study, 4857 participants aged over 20 years with information on smoking and confounders in the third phase (2005-2008) were included, and the MS was assessed in the fifth phase (2011-2014). IPTW and PS matching were used to adjust for confounders. RESULTS: Based on average treatment effect (ATE) estimates, smoking decreased the risk of hypertension (RR: 0.62; 95% CI: 0.43, 0.88), but increased the risk of low HDL cholesterol (1.20; 0.98, 1.48). Similarly, the average treatment effect in the treated (ATT) estimates using IPTW and PS matching suggested that smoking decreased the risk of hypertension (0.63; 0.52, 0.76, and 0.68; 0.54, 0.85), and increased the risk of low HDL cholesterol (1.24; 1.07, 1.43, and 1.28; 1.06, 1.54), respectively. CONCLUSIONS: Smoking seems to increase the risk of low HDL cholesterol but decreases the risk of hypertension.